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发表于 2010-12-17 13:52:18
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Project: Mtb, Myctu, Mycle & Myc
Mycobacterium tuberculosis is the the causative agent of tuberculosis (TB) which is a world-wide pandemic that is contagious and spreads through the air. Scaringly, more than two billion people, equal to one third of the world’s total population, are infected with TB bacilli. Even worse, multidrug-resistant TB (MDR-TB) is a form of TB that does not respond to the standard treatments using first-line drugs and is present in virtually all countries surveyed by WHO and its partners. Strikingly, a total of 1.77 million people died from TB in 2007, equal to about 4800 deaths a day which makes TB one of the world's major causes of death.
Since it is known that certain non-coding RNAs (ncRNAs) are required to control the ability of many pathogens to infect their hosts, in this project we undertake an exhaustive search to map all ncRNAs known to date in this organism. Moreover, including the leprosy-causing agent Mycobacterium leprae, we extend our bioinformatic analyses to all fully sequenced strains of the genus Mycobacterium and also compare pathogenic versus non-pathogenic strains to possibly identify ncRNA-based differences that might be involved in virulence processes. To validate the biological and medical relevance of our computational investigations, laboratory experiments are performed in cooperation with our research partners in India. It is clear that the potentially possible identification of a ncRNA which is essential for pathogenicity of this organism may represent an excellent novel drug target to battle TB in the future.
结核分支杆菌(Mycobacterium tuberculosis)是造成结核病的主要病原体。结核病是一种全球范围内流行的,能够通过空气传播的传染性疾病。令人毛骨悚然的事实是,全世界超过有20亿,约占世界总人口的三分之一的人感染有结核分枝杆菌。更糟的是,多药物抵抗性的结核病菌(MDR-TB)是一种使用一般的一线药物治疗不起任何作用的结核病菌,且根据世界卫生组织(WHO)的调查,这种病菌事实上已经存在于所有该组织及其成员调查过的国家内。2007年,有177万人惨死于结核病,相当于每天致死4800人。这使得结核病已经成为世界上首要的死亡原因之一。
由于我们已经知道,特定的非编码RNA(ncRNAs)是很多病原提感染宿主所必须的,在这个项目中,我们试图进行一种地毯式比对搜寻,将该病原的迄今已知的所有ncRNAs都进行定位。此外,我们将我们的生物信息学研究扩展到了所有已经完整测定了基因组的分支杆菌属(Mycobacterium)的其他物种上,比如造成麻风病的麻风杆菌(Mycobacterium leprae)等,将致病的和非致病的品系进行比对,以试图鉴定出ncRNA上的差别,找到与致病性过程相关的ncRNA。为了验证我们计算方法的适用性,我们的研究伙伴同时在印度进行实验室工作(以验证计算的准确性)。显然,如果能够鉴定出在结核杆菌致病性中起关键作用的ncRNA,那么在将来就有可能造就出一种有效的击败结核病的新药
References:
参考文献(不翻了,表示无爱)
Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE 3rd, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537-44.
Camus JC, Pryor MJ, Médigue C, Cole ST. Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology. 2002 Oct;148(Pt 10):2967-73.
Terwilliger TC, Park MS, Waldo GS, Berendzen J, Hung LW, Kim CY, Smith CV, Sacchettini JC, Bellinzoni M, Bossi R, De Rossi E, Mattevi A, Milano A, Riccardi G, Rizzi M, Roberts MM, Coker AR, Fossati G, Mascagni P, Coates AR, Wood SP, Goulding CW, Apostol MI, Anderson DH, Gill HS, Eisenberg DS, Taneja B, Mande S, Pohl E, Lamzin V, Tucker P, Wilmanns M, Colovos C, Meyer-Klaucke W, Munro AW, McLean KJ, Marshall KR, Leys D, Yang JK, Yoon HJ, Lee BI, Lee MG, Kwak JE, Han BW, Lee JY, Baek SH, Suh SW, Komen MM, Arcus VL, Baker EN, Lott JS, Jacobs W Jr, Alber T, Rupp B. The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology. Tuberculosis (Edinb). 2003;83(4):223-49.
Chhabria M, Jani M, Patel S. New frontiers in the therapy of tuberculosis: fighting with the global menace. Mini Rev Med Chem. 2009 Apr;9(4):401-30. |
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